Herpes simplex keratitis (HSK) caused by herpes simplex virus type 1 (HSV-1) is a major cause of infectious corneal blindness in developed countries. The disease reflects a variable combination of viral replication, immune-mediated inflammation and neurotrophic dysfunction, whose respective contributions determine both the clinical presentation and therapeutic strategy. Standard management relies on antiviral agents to suppress viral replication, corticosteroids to control immune stromal involvement and ocular surface optimisation to address chronic inflammation and neurotrophic impairment. Refractory forms, defined by a lack of clinical improvement despite appropriate treatment, require reassessment of adherence, pharmacokinetic exposureand underlying pathophysiology. In such cases, antiviral dose adjustment, the use of steroid-sparing immunomodulators and rigorous control of ocular surface inflammation are essential. Neurotrophic keratopathy may benefit from growth factor-based therapies, autologous serum, recombinant nerve growth factor or scleral lenses. The emergence of acyclovir-resistant HSV-1 strains, particularly in immunocompromised or long-term treated patients, represents an increasing concern. In these situations, alternative agents such as trifluridine, foscarnet or more recently, helicase-primase inhibitors, including amenamevir, have demonstrated clinical efficacy. The new strategies outlined here will all provide benefit in treating the drivers of refractory HSK, to quickly resolve and reduce risk of recurrence, providing new opportunities to prevent vision loss in refractory and antiviral-resistant cases.

Varicella zoster virus (VZV) is an exclusively human alphaherpesvirus that infects >90% of the global population. Primary infection typically causes varicella (chickenpox), after which VZV establishes lifelong latency in ganglionic neurons along the entire neuroaxis. Virus reactivation, typically triggered by age-associated immune dysfunction or immune suppressive conditions, produces herpes zoster (shingles) that can be complicated by post-herpetic neuralgia. In limited instances, VZV reactivation (and rarely primary infection) also produces multisystem disease including vasculopathy, cranial neuropathies, myelopathy and cardiovascular or gastrointestinal complications; these complications can occur without, or temporally dissociated from, rash. Diagnosis of varicella or herpes zoster relies on clinical presentation of a disseminated or dermatomal-distribution rash, respectively; diagnosis of VZV infection (owing to replicating virus) is more challenging when cases are atypical and/or occur without rash. Prevention strategies include administration of live attenuated varicella vaccine and recombinant zoster vaccine. VZV infection is treated with antiviral drugs including oral valacyclovir (drug of choice), famciclovir, acyclovir or amenamevir; for severe or disseminated disease, intravenous acyclovir or foscarnet (when other drugs fail) are used. Critical challenges remain in recognizing and diagnosing atypical presentations, developing novel therapeutics, establishing the causal role of VZV in vascular and neurodegenerative disease, and achieving broader vaccine implementation worldwide.

Pritelivir, a novel helicase-primase inhibitor, has successfully completed a global Phase 3 trial for refractory herpes simplex virus (HSV) infections in immunocompromised patients. This case report is the first clinical use of pritelivir in Herpes simplex encephalitis (HSE). An allogeneic hematopoietic cell transplant recipient developed HSE and was treated with acyclovir. After 1.5 months, while still on valacyclovir prophylaxis, HSE relapsed, confirmed by Magnetic Resonance Imaging (MRI) and HSV1 DNA detection in cerebrospinal fluid (CSF). Following transient response to acyclovir and foscarnet, combined pritelivir/acyclovir treatment was initiated in this comatose patient with cerebral edema and necrosis. Clinical improvement occurred with increased alertness and motor activity, enabling discharge to rehabilitation. MRI showed no further progression, and CSF HSV DNA load became undetectable. No relevant adverse effects were observed. Pritelivir plasma and CSF concentrations exceeded the 50% effective concentration for HSV1. This case highlights the potential of pritelivir for treating HSE.

Consider human herpesvirus 6 (HHV-6) in immunocompetent adults with viral meningitis when standard tests are negative. Qualitative CSF PCR requires cautious interpretation because it cannot exclude chromosomally integrated HHV-6. Serial CSF improvement and rapid clinical recovery may support probable self-limited infection and help avoid unnecessary ganciclovir or foscarnet therapy.

Background/Objectives: Cytomegalovirus (CMV) reactivation is a major cause of morbidity and mortality in allogeneic hematopoietic stem cell transplant (allo-HCT) recipients. Letermovir is used to prevent infections, but it is not available in many countries. Ganciclovir and valganciclovir carry a risk of bone marrow suppression. Foscarnet is frequently used as a bone marrow-sparing alternative; however, its clinical utility is constrained by nephrotoxicity. In this study, we aimed to evaluate the efficacy and renal safety of foscarnet and to identify factors associated with acute kidney injury (AKI) occurring during foscarnet treatment. Methods: This real-world, retrospective, single-center cohort study included 40 adult allo-HCT recipients treated with foscarnet for CMV reactivation between May 2022 and February 2025. Results: CMV polymerase chain reaction (PCR) negativity was achieved in 90% of patients, with a median time to PCR negativity of 10 (4-28) days. AKI occurred in 42.5% of patients, and 12.5% required hemodialysis. Foscarnet treatment was associated with a significant increase in serum creatinine levels and significant reductions in potassium, calcium, and magnesium concentrations (p < 0.05 for all). In univariable logistic regression analysis, myeloablative conditioning was associated with higher odds of AKI (OR 10.29, 95% CI 1.15-91.63; p = 0.037), while male sex showed numerically higher odds that did not reach conventional statistical significance (OR 4.28, 95% CI 0.96-19.01; p = 0.056). Conclusions: Among allo-HCT recipients treated with foscarnet, virological clearance was frequently observed, while AKI and electrolyte disturbances were common. These findings suggest that close renal and electrolyte monitoring may be warranted. However, given the retrospective, single-center design, small sample size, and absence of a comparator group, the findings should be interpreted cautiously and confirmed in larger prospective comparative studies.

Human herpesvirus 6 (HHV-6) reactivation is a rare but serious complication of chimeric antigen receptor T-cell (CAR-T) therapy that can overlap with immune effector cell-associated neurotoxicity syndrome (ICANS) or cytokine release syndrome (CRS), making diagnosis and management challenging. We describe a 68-year-old man with relapsed/refractory IgA kappa multiple myeloma who received multiple prior therapies, including CyBorD, mVRD-lite, Dara-CyBorD, VD-ACE, and KPd, before undergoing lymphodepleting chemotherapy and CAR-T infusion. Early after infusion he developed grade 2 CRS and ICANS that improved with tocilizumab and corticosteroids, followed by recurrent encephalopathy with progressive neurologic decline. Initial infectious evaluation was negative, but repeat cerebrospinal fluid (CSF) and plasma polymerase chain reaction testing revealed HHV-6 reactivation. Antiviral therapy with foscarnet, later switched to ganciclovir, was initiated with corticosteroids and intravenous immunoglobulin. Although repeat CSF testing showed transient viral clearance, neurologic function continued to decline, and brain MRI demonstrated findings consistent with ICANS, including scattered white matter signal abnormalities and dural enhancement. Despite aggressive management, the patient developed multiorgan failure and died. This case illustrates the diagnostic complexity of HHV-6 reactivation during CAR-T therapy, where overlapping clinical and radiologic features with ICANS can obscure recognition; profound immunosuppression from prior treatment and CAR-T-induced immune dysregulation likely predisposed to viral reactivation. HHV-6 reactivation is a critical, underrecognized cause of neurotoxicity after CAR-T therapy, and clinicians should maintain a high index of suspicion in patients with delayed or atypical neurotoxicity, since early virologic testing and prompt antiviral therapy may improve outcomes in this vulnerable population.